Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Mendelics | RCV000709396 | SCV000839084 | uncertain significance | Hereditary diffuse gastric adenocarcinoma | 2018-07-02 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000709396 | SCV002262864 | uncertain significance | Hereditary diffuse gastric adenocarcinoma | 2021-05-04 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). This sequence change replaces isoleucine with valine at codon 326 of the CDH1 protein (p.Ile326Val). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and valine. This variant has not been reported in the literature in individuals with CDH1-related conditions. ClinVar contains an entry for this variant (Variation ID: 584916). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant disrupts the p.Ile326 amino acid residue in CDH1. Other variant(s) that disrupt this residue have been observed in individuals with CDH1-related conditions (PMID: 28487081), which suggests that this may be a clinically significant amino acid residue. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. |
| Color Diagnostics, |
RCV003584733 | SCV004360461 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-09-07 | criteria provided, single submitter | clinical testing | This missense variant replaces isoleucine with valine at codon 326 of the CDH1 protein. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |